Role of Protein Corona in the Fate of Hydrophilic Polymeric Nanoparticles: A Fundamental Study

纳米粒子是尺寸在纳米数量级的物质粒子。在生物环境中，纳米粒子获得一层蛋白质，称为电晕，其电晕的组成严重影响纳米粒子的生物命运。尽管在过去的十年中已经进行了各种各样的研究来了解纳米颗粒的蛋白质电晕，但人们对常用的亲水（即“亲水”）生物聚合物纳米颗粒上形成的蛋白质电晕知之甚少。该项目的研究小组将研究针对一些亲水性生物聚合物形成的蛋白质冠。目的是解码蛋白质冠状体的组成，并将鉴定的蛋白质与纳米颗粒的表面化学联系起来。然后，研究人员将利用这些知识进一步了解纳米颗粒的生物学命运。这项研究将增强我们对蛋白质冠的基本理解，确定促进或减少细胞摄取的关键蛋白质，并指导设计更好、更安全的纳米颗粒，用于广泛的应用。该研究项目是研究生和本科生进行前沿研究的训练基地。研究团队将通过各种校园项目招募本科生，特别是在STEM领域代表性不足的学生。从这项工作中获得的知识将通过在国际会议上的发言、为新课程编制课程和外联活动来传播。纳米颗粒上的蛋白质电晕已被证明是纳米颗粒生物学命运的决定因素。目前，大多数研究集中在模型疏水聚苯乙烯或无机纳米颗粒体系上的电晕形成。人们对最常用的亲水生物聚合物纳米颗粒上形成的蛋白质电晕知之甚少。本研究的目的是利用一个定义良好的水凝胶纳米粒子系统，解码针对一些亲水性生物聚合物形成的蛋白质冠的组成，并将鉴定的蛋白质与纳米粒子的表面化学和命运联系起来。磁性纳米颗粒将被封装在水凝胶纳米颗粒中，以便利用磁场轻松收集蛋白质电晕。蛋白质冠状体的组成将使用最先进的蛋白质组学分析来解码，以提供血浆蛋白与这些亲水性聚合物相互作用的见解。这些吸附蛋白对纳米颗粒命运的影响将通过巨噬细胞和树突状细胞的细胞摄取实验进一步研究。对蛋白质电晕的基本理解将指导设计更好和更安全的纳米粒子，用于广泛的生物医学和工程应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Nanoparticles are particles of matter with dimensions on the order of nanometers. In a biological environment, nanoparticles acquire a layer of proteins, called a corona, and the composition of their corona critically affects the biological fate of nanoparticles. Although a variety of studies have been done to understand the protein corona of nanoparticles over the past decade, little is known about protein corona formed on commonly used hydrophilic (i.e., "water loving") biopolymer nanoparticles. The research team on this project will study the protein corona formed against a number of hydrophilic biopolymers. The objectives are to decode the compositions of the protein coronas and to correlate the identified proteins with the surface chemistry of the nanoparticles. The researchers will then use this knowledge to further understand the biological fate of the nanoparticles. This research will enhance our fundamental understanding of protein corona, identify key proteins responsible for the promotion or reduction of cellular uptake, and guide the design of better and safer nanoparticles for a broad range of applications. The research project serves as a training ground for graduate and undergraduate students to perform cutting edge research. The research team will recruit undergraduate students, particularly students underrepresented in STEM fields, through various on-campus programs. Knowledge from this work will be disseminated through presentations at international conferences, the development of curricula for new courses, and outreach activities. Protein corona on nanoparticles have been shown to be determinant for the biological fate of nanoparticles. At present, most research has focused on corona formation on model hydrophobic polystyrene or inorganic nanoparticle systems. Little is known about protein corona formed on the most commonly used hydrophilic biopolymer nanoparticles. The objectives of this study are to decode the compositions of protein coronas formed against a number of hydrophilic biopolymers using a well-defined, hydrogel nanoparticle system and to correlate the identified proteins with the surface chemistry and fate of nanoparticles. Magnetic nanoparticles will be encapsulated inside the hydrogel nanoparticles to enable the facile harvesting of protein corona using a magnetic field. The compositions of protein coronas will be decoded using state-of-the-art proteomic analysis to provide insights into the interaction of plasma proteins with these hydrophilic polymers. The impact of these adsorbed proteins on the fate of the nanoparticles will be investigated further through cellular uptake experiments using both macrophage and dendritic cells. A fundamental understanding of protein corona will guide the design of better and safer nanoparticles for a wide range of biomedical and engineering applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.